Menin inhibitors for adult acute myeloid leukemia: 2025 update

Menin inhibitors are a relatively new class of drugs that reverse oncogenesis and induce leukemic cell differentiation by blocking the interaction between the MEN1 gene product (menin) and lysine (K)-methyltransferase 2 (KMT2A). This is relevant in 50-70% of acute myeloid leukemia (AML) subsets driven by overexpression of the HOXA9/MEIS1 pathway. These patients have dismal outcomes with current options, especially in the relapsed/refractory setting.

Here, we discuss menin pathobiology, the available and emerging clinical data for menin inhibitors, clinical nuance related to their use, and the current unmet needs that may guide future endeavors for this drug class. A literature search was conducted using PubMed/MEDLINE, Embase, and Web of Science databases. The search included articles published in English up to 25 August 2025. Keywords and Medical Subject Headings (MeSH) related to 'menin inhibitors' were combined using Boolean operators (AND, OR). Additionally, abstracts from major hematology conferences were reviewed, and the clinicaltrials.gov registry was queried for active trials as well.

Menin inhibitor approval/use is expanding into other HOX-driven subtypes (e.g. NPM1, NUP98r), as a frontline option and in combination settings. Monitoring for differentiation syndrome, QT interval prolongation, recognizing pseudo-progression, and supportive care needs remains essential to maximize patient benefit.